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Unexpected One‐Step Formation of Iodo[1,3]dioxolo[4,5‐ c ]pyridine Derivatives by a Hofmann–Löffler–Freytag Reaction: Studies on the Synthesis of a Pyridine‐Containing Macrocycle
Author(s) -
Lechel Tilman,
Podolan Gabriel,
Brusilowskij Boris,
Schalley Christoph A.,
Reissig HansUlrich
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201200564
Subject(s) - chemistry , pyridine , halogenation , medicinal chemistry , iodine , polymer chemistry , acetylide , organic chemistry
Abstract During attempts to prepare functionalized 5‐iodopyridine derivatives the unexpected formation of iodo[1,3]dioxolo[4,5‐ c ]pyridines was discovered. The conversion of 3‐alkoxypyridin‐4‐ols into the corresponding 5‐iodo compounds was achieved by reaction with one equivalent of iodine or tetramethylammonium dichloroiodate under basic conditions. When three equivalents of iodine were used in chlorinated solvents, after 5‐iodination, subsequent reaction of the 3‐alkoxy group took place to form a 1,3‐dioxolane ring with the 4‐hydroxyl group. Generation of the resulting iodo[1,3]dioxolo[4,5‐ c ]pyridines is explained by a radical process known as the Hofmann–Löffler–Freytag reaction. Two 6‐ethynylpyridine derivatives were examined in the iodination process to establish a route to pyridine‐containing macrocycles. The pentasubstituted 5‐iodopyridine derivative 21 could be prepared; however, attempts to achieve cyclotrimerization of this building block under different conditions were not successful. Reaction of 21 with copper chloride allowed isolation of a copper acetylide 22 , which aggregates to a triangular trimeric complex containing four copper(I) ions such as [ 23· Cu] + as monitored by ESI mass spectrometry.